Mutations in ANKS6 cause a Nephronophthisis‐Like Phenotype with End Stage Renal Disease

<p>Nephronophthisis (NPHP) is one of the most common genetic causes of chronic kidney disease (CKD); however the underlying genetic abnormalities have been established in less than 50% of cases. We performed genome-wide analysis followed by targeted re-sequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 as the cause of an NPHP-like phenotype. Furthermore, we identified 4 additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic glomerulonephritis, interstitial nephritis or unknown etiology. We demonstrated expression of ANKS6 in human embryonic kidneys and showed that both total and active β-catenin were increased in pre-cystic tubuli in Cy/+ rats, indicating strong activation of the Wnt pathway</p